Haloalkyl heteroaryl benzamide compounds

ABSTRACT

A new class of haloalkyl heteroaryl benzamides is described. These compounds show strong activity against hepatitis viruses.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Reissue Application of U.S. Pat. No. 9,126,992,which issued on Sep. 8, 2015 from U.S. application Ser. No. 14/658,409,which is a Divisional of U.S. application Ser. No. 12/777,383, filed May11, 2010, which issued as U.S. Pat. No. 8,846,727, on Sep. 30, 2014,which claims benefit of U.S. Provisional Application No. 61/177,626,filed May 12, 2009, the entire contents of which are incorporated hereinby reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was funded by NIAID contract NO1-AI-30046. The UnitedStates government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention is directed to new heterocyclic compounds,pharmaceutically acceptable salts thereof, compositions comprising suchcompounds and salts, and methods of using those compounds, salts, andcompositions for the treatment of viral disease. It is also directed tomethods of inhibition of viral pathogen activity in humans and animals.It is also directed to treatment of hepatitis C virus (HCV), hepatitis Bvirus (HBV), and related viral pathogen infection in humans and animals.

BACKGROUND

The present application relates generally to the field of thiazolidecompounds. In particular, the application relates tohaloalkyl-substituted thiazolide compounds.

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are major publichealth problems, causing more than an estimated 500 million chronicinfections worldwide. Both viruses cause significant progressive liverdisease and are major risk factors for primary hepatocellular carcinoma.Current standards of care for both HBV and HCV infections, whileeffective in many cases, are sub-optimal and fail to produce either avirologic or a clinical ‘cure’ in most. The development ofdrug-resistance in HBV, including strains carrying resistance tomultiple currently used agents, is an emerging clinical problem, anddrug-resistance for future HCV therapies is predicted to be asignificant clinical issue

SUMMARY

This invention provides novel compounds and pharmaceutical compositionsthat treat viral pathogens, as well as methods of synthesizing and usingthe compounds to treat and inhibit viral infection. The compounds ofthis invention are haloalkyl heteroaryl benzamides

In one embodiment, this invention provides compounds of Formula I and

pharmaceutically acceptable salts thereofwherein:

R₁ through R₅ and R₁₀ are, independently chosen hydrogen, CN, NO₂,halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy,alkynyloxy, alkoxyalkynyl, alkenyloxyalkyl, alkenyloxyalkenyl,alkenyloxyalkynyl, alkynyloxyalkyl, alkoxyalkylamino, hydroxyalkyl,acyl, acyloxy, aroyloxy, arylalkanoyloxy, arylalkenoyloxy,heteroaroyloxy, heteroarylalkanoyloxy, heteroarylalkenoyloxy,alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl,heteroarylalkoxycarbonyl, alkoxycarbonyloxy, carbamoyl, carbamoyloxy,alkylamino, dialkylamino, alkylaminoalkyl, amido, alkylamido,dialkylamido, perhaloalkoxy, alkylthio, perhaloalkylthio,alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, alkenylsulfonyl,alkynylsulfonyl, cycloalkylsulfonylalkyl, cycloalkylalkylsulfonylalkyl,arylsulfonyl, arylalkylsulfonyl, arylalkenylsulfonyl,heteroarylsulfonyl, heteroarylalkylsulfonyl, heteroarylalkenylsulfonyl,aryl, aryloxy, arylthio, arylalkylthio, alkylthio, perhaloalkylthio,arylamino, arylalkylamino, arylalkenyl, arylalkynyl, heteroaryl,heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroaryloxy,heteroarylalkoxy, heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, or heterocycloalkenyloxy, alloptionally substituted as described below

wherein R₆ is selected from the group consisting of haloalkyl,perhaloalkyl, haloalkoxy, perhaloalkoxy, S(O)_(m)C(R₇R₈)_(n)CF₃, andC(R₇R₈)_(n)CF₃;

wherein W, X and Y are, independently, S, O, N, NR₉ or CR₁₀ where atleast two of W, X, and Y are S, O, N, or NR₉;

wherein R₇, R₈, and R₉ are independently selected from the groupconsisting of hydrogen, fluoro, chloro, alkyl, perhaloalkyl, aryl,arylalkyl, heteroaryl and heteroarylalkyl, or R₇ and R₈, together withthe atoms to which they are attached, are joined to form a 3- to8-membered cycloalkyl ring or a 4- to 8-membered heterocycloalkyl,either ring optionally substituted as described below;

m is an integer between 0 and 2; and

n is an integer between 0 and 5;

or a pharmaceutically acceptable salt or ester thereof

These compounds are useful in treating disorders and conditions causedby viral pathogens.

In another embodiment, this invention provides or contemplates acomposition comprising a compound of formula I and a carrier.

In another embodiment, this invention provides or contemplates apharmaceutical composition comprising a compound of Formula I and apharmaceutically acceptable carrier.

In another embodiment, this invention provides or contemplates a methodof treatment of viral infection comprising administering to a human oranimal afflicted with viral infection a therapeutically effective amountof a compound of Formula I.

In a more specific embodiment, this invention provides or contemplates amethod of treatment of HCV infection comprising administering to a humanor animal afflicted with viral infection a therapeutically effectiveamount of a compound of Formula I.

In a more specific embodiment, this invention provides or contemplates amethod of treatment of HBV infection comprising administering to a humanor animal afflicted with viral infection a therapeutically effectiveamount of a compound of Formula I.

In other embodiments, the present invention provides or contemplatesmethods for inhibiting or modulating a viral pathogen. In otherembodiments, the present invention provides or contemplates methods fortreating a viral-mediated disorder in a patient in need of suchtreatment comprising administering to said patient a therapeuticallyeffective amount of a compound or composition of compounds of thisinvention. In other embodiments, this invention provides or contemplatesmethods for treating HCV, HBV, and other viral infections comprisingadministering pharmaceutical compositions of the invention to a patientin need thereof. For example, the patient may have a chronic HCVinfection. The present invention also contemplates the use of compoundsdisclosed herein for use in the manufacture of a medicament for thetreatment of a disease or condition ameliorated by the inhibition ormodulation of viral activity.

DETAILED DESCRIPTION

Unless otherwise specified, “a” or “an” means “one or more.”

In one embodiment, this invention provides or contemplates a compound ofFormula I, wherein R₁ through R₅ are, independently, hydrogen, cyano,fluoro, chloro, bromo, hydroxy, alkyl, alkoxy, aryloxy, aroyloxy,heteroaroyloxy, heteroarylalkanoyloxy, alkoxycarbonyloxy, carbamoyloxy,alkylamino, haloalkyl, perhaloalkyl, perhaloalkylthio, perhaloalkoxy,alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, orcycloalkylalkylsulfonyl, all optionally substituted as described below.

R₆ is selected from the group consisting of perhaloalkyl,S(O)_(m)C(R₇R₈)_(n)CF₃, and C(R₇R₈)_(n)CF₃;

R₇, R₈, and R₉ are, independently, hydrogen, fluoro, chloro, alkyl, orperhaloalkyl, any of which may be optionally substituted;

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, alkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, heteroarylalkoxycarbonyl, carbamoyl, alkylamino,amido, alkylamido, dialkylamido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl,alkylsulfonamido, aryl, arylalkyl, aryloxy, arylalkoxy, arylthio,arylalkylthio, arylamino, arylalkylamino, heteroaryl, heteroarylalkyl,heteroaryloxy, heteroarylalkoxy, heteroarylamino, heteroarylalkylamino,heteroarylthio, heteroarylalkylthio, heteroarylalkylamino,heterocycloalkyl, heterocycloalkenyl, heterocycloalkoxy, andheterocycloalkenyloxy; and

m and n are, independently, integers equal to 0, 1, or 2.

In a more specific embodiment, this invention provides or contemplates acompound of Formula I wherein R₁, R₂, or R₃ are, independently, hydroxy,acyloxy, aroyloxy, arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy,heteroarylalkanoyloxy, heteroarylalkenoyloxy, alkoxycarbonyloxy, orcarbamoyloxy, any of which may be optionally substituted.

In another more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein one of R₁, R₂ and R₃ ishydroxy or acetoxy.

In another more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein either R₃ or R₄ is halogen.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein one of R₁, R₂ and R₃ ishydroxy or acetoxy and wherein R₄ is halogen.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein R₁ is hydroxy or acetoxyand wherein R₂, R₃ or R₄ is halogen.

In another more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein R₃ or R₄ is methyl ormethoxy.

In another more specific embodiment, this invention provides orcontemplates a compound of Formula I wherein one of R₁, R₂ and R₃ ishydroxy or acetoxy.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is selected from the group consistingof perhaloalkyl and C(R₇R₈)_(n)CF₃, wherein R₇ and R₈ are as definedabove.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is perfluoroalkyl or perchloroalkyl.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is perfluoro or perchloro C₁-C₃ alkyl.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is trifluoromethyl.

In another embodiment this invention provides or contemplatespharmaceutical compositions comprising one or more compounds of thepresent invention together with a pharmaceutically acceptable carrier(e.g., a diluent or excipient). It other embodiments this inventionprovides or contemplates methods of making and using the compounds andcompositions. In more specific embodiments, the invention provides orcontemplates pharmaceutical compositions which comprise therapeuticallyeffective amounts of the compound of this invention and methods of usingsuch compositions for treating HCV, HBV, and other viral infections.

In one subgeneric embodiment, this invention provides or contemplates acompound of Formula I in which W is O and either X or Y is N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is O and both X and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is S and either X or Y is N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is S and both X and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N and either X or Y is O.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N and either X or Y is S.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N and either X or Y is N or NR₉

In another embodiment, this invention provides or contemplates acompound of Formula I in which two of W, X, and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W, X, and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is CR₁₀, one of X or Y is O, and theother is N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is CR₁₀, one of X or Y is O and theother is N or NR₉.

In one subgeneric embodiment, this invention provides or contemplates acompound of Formula I in which W is O and either X or Y is N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is O and both X and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is S and either X or Y is N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is S and both X and Y are N or NR₉.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N or NR₉ and either X or Y is O.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N or NR₉ and either X or Y is S.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N; either X or Y is N or NR₉; and R₆is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N; either X or Y is N or NR₉; and R₆is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N, in which either X or Y is N orNR₉, and wherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W is N, in which either X or Y is N orNR₉, and wherein R₆ is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which two of W, X, and Y are N or NR₉ andwherein R₆ is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which two of W, X, and Y are N or NR₉ andwherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W, ×, and Y are N or NR₉ and wherein R₆is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which W, X, and Y are N or NR₉ and wherein R₆is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which one of X or Y is O and the other is N orNR₉ and wherein R₆ is methyl, fluoromethyl, or trifluoromethyl.

In another embodiment, this invention provides or contemplates acompound of Formula I in which one of X or Y is O and the other is N orNR₉ and wherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein one of X or Y is O and the other is N orNR₉ and wherein R₆ is methyl, fluoromethyl, or trifluoromethyl.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein one of X or Y is O and the other is N orNR₉ and wherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is methyl, fluoromethyl, ortrifluoromethyl.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I in which three of R₁-R₅— are H.

In another embodiment, this invention provides or contemplates acompound of Formula I in which two of R₂-R₅— are H.

In another embodiment, this invention provides or contemplates acompound of Formula I in which three of R₂-R₅— are H.

In another embodiment, this invention provides or contemplates acompound of Formula I in which R₂-R₅— are H.

In another embodiment, this invention provides or contemplates acompound of Formula I in which one of R₁-R₅ is O—R₁₂, where R₁₂ is H orC₁-C₆ alkanoyl, the latter optionally substituted with 1-3 halogens

In another embodiment, this invention provides or contemplates acompound of Formula I in which R₆ is C₁-C₃ alkyl, optionally substitutedwith 1-3 halogens.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is methyl, fluoromethyl, ortrifluoromethyl.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is SO₂CF₃ or SO₂CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₆ is CF₂CH₃, CF₂CF₃ or CH₂CF₃.

In another embodiment, this invention provides or contemplates acompound of Formula I wherein R₁ is hydroxy or alkanoyloxy.

In a more specific embodiment, this invention provides or contemplates acompound of Formula I wherein R₁ is hydroxy or C₁-C₃ alkanoyloxy.

In another embodiment, this invention provides or contemplates acompound of Formula II

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In additional embodiments, this invention provides or contemplates acompound of Formula II wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula II wherein

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In a more specific embodiment, this invention provides or contemplates acompound of Formula II wherein R₁ is hydroxy or C₁-C₃ alkanoyloxy.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula II wherein R₁ is hydroxy or acetoxy;and

and 3, 4, or all of R₂-R₅ and R₁₀ are hydrogen.

In a still more specific embodiment, this invention provides orcontemplates the following compounds of Formula I:2-(5-(trifluoromethyl)thiazol-2-ylcarbamoyl)phenyl acetate and2-hydroxy-N-(5-(trifluoromethyl)thiazol-2-yl)benzamide.

In another subgeneric embodiment, this invention provides orcontemplates a compound of Formula III:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In a more specific embodiment, this invention provides or contemplates acompound of Formula III wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula III wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In another more specific embodiment, this invention provides orcontemplates a compound of Formula III wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In a more specific embodiment, this invention provides or contemplates acompound of Formula III wherein R₁ is hydroxy or C₁-C₃ alkanoyloxy.

In another embodiment, this invention provides or contemplates acompound of Formula III wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and 3, 4,or all of

R₂-R₅ and R₁₀ are hydrogen.

In another subgeneric embodiment, this invention provides orcontemplates a compound of Formula IV:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In a more specific embodiment, this invention provides or contemplates acompound of Formula IV wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,alkyl, aryloxycarbonyl, heteroaryloxycarbonyl, carbamoyl, amido,dialkylamido, perhaloalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocycloalkyl, and heterocycloalkenyl; an with the proviso that whenR₄ is Br, R₁₀ may not be unsubstituted phenyl.

In a more specific subgeneric embodiment, this invention provides orcontemplates a compound of Formula IV wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula IV wherein R₁ is hydroxy or acetoxy;and 3, 4, or all of R₂-R₅ and R₁₀ are hydrogen.

Examples of this more specific embodiment include the compounds include2-(4-(trifluoromethyl)thiazol-2-ylcarbamoyl)phenyl acetate and2-hydroxy-N-(4-(trifluoromethyl)thiazol-2-yl)benzamide.

In another embodiment, this invention provides or contemplates acompound of Formula V:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In a more specific embodiment, this invention provides or contemplates acompound of Formula V wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In additional embodiments, this invention provides or contemplates acompound of Formula V wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In more specific embodiments, this invention provides or contemplatescompounds of Formula V wherein:

R₁ is hydroxy or acetoxy; and

3, 4, or all of R₂ through R₅ and R₁₀ are hydrogen.

In another embodiment, this invention provides or contemplates acompound of Formula VI:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In a more specific embodiment, this invention provides or contemplates acompound of Formula VI wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula VI wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In more specific embodiments, this invention provides or contemplatescompounds of Formula VI wherein R₁ is hydroxy or acetoxy; and 3, 4, orall of R₂ through R₅ and R₁₀ are hydrogen.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula VI wherein:

R₁ is hydroxy or acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In additional embodiments, this invention provides or contemplates acompound of Formula VII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In more specific subgeneric embodiments, the invention provides orcontemplates a compound of Formula VII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In more specific embodiments, this invention provides or contemplates acompound of Formula VII wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In more specific embodiments, this invention provides or contemplatescompounds of Formula VII wherein R₁ is hydroxy or acetoxy; and 3, 4, orall of R₂ through R₅ and R₁₀ are hydrogen.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula VII wherein:

R₁ is hydroxy or acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In another embodiment, this invention provides or contemplates acompound of Formula VIII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy;

In some embodiments, the compounds of the present invention havestructural Formula VIII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula VIII wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In more specific embodiments, this invention provides or contemplatescompounds of Formula VIII wherein R₁ is hydroxy or acetoxy; and 3, 4, orall of R₂ through R₅ and R₁₀ are hydrogen.

In a still more specific embodiment, this invention provides orcontemplates a compound of Formula VIII wherein: R₁ is hydroxy oracetoxy; and R₂ through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula IX:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy;

In some embodiments, the compounds of the present invention havestructural Formula IX wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula IX wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula IX wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and R₂through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula X:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula X wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula X wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In other embodiments, the compounds of the present invention havestructural Formula X wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is alkyl, which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XI:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XI wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In further embodiments, the compounds of the present invention havestructural Formula XI wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XI wherein R₁ is chosen from the group consisting ofhydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is alkyl, which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XII wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is alkyl, which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XIII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy;

In some embodiments, the compounds of the present invention havestructural Formula XIII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In some embodiments, the compounds of the present invention havestructural Formula XIII wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XIII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is alkyl, which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XIV:

wherein:

R₁ through R₅ or, hydrogen, CN, F, Cl, Br, hydroxy, alkyl, cycloalkyl,cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkylalkoxy,hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy, arylalkenoyloxy,heteroaroyloxy, heteroarylalkanoyloxy, heteroarylalkenoyloxy,alkoxycarbonyloxy, carbamoyloxy, alkylamino, haloalkyl, perhaloalkyl,perhaloalkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl,cycloalkylsulfonyl, and cycloalkylalkylsulfonyl, any of which may beoptionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XIV wherein:

R₁ and R₂ are, independently, hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, or carbamoyloxy, any of whichmay be optionally substituted;

R₃ is selected from the group consisting of acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XIV wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XIV wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XV:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XV wherein:

R₁ and R₂ are, independently, hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, or carbamoyloxy, any of whichmay be optionally substituted;

R₃ is selected from the group consisting of acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XV wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XV wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XVI:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XVI wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In further embodiments, the compounds of the present invention havestructural Formula XVI wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XVI wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XVII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XVII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XVII wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XVII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ and R₁₀ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XVIII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy;

In some embodiments, the compounds of the present invention havestructural Formula XVIII wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XVIII wherein:

R₁ is chosen from the group consisting of hydroxy, aryloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XVIII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is methyl.

In certain embodiments, the compounds of the present invention havestructural Formula XIX:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted;

R₉ is selected from the group consisting of hydrogen, fluoro, chloro,alkyl, and perhaloalkyl, any of which may be optionally substituted; and

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl,cycloalkoxy, cycloalkylalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,carbamoyl, alkylamino, amido, alkylamido, dialkylamido, perhaloalkyl,alkylthio, alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, alkylsulfonamido, aryl, arylalkyl, aryloxy,arylalkoxy, arylthio, arylalkylthio, arylamino, arylalkylamino,heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy,heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heteroarylalkylamino, heterocycloalkyl,heterocycloalkenyl, heterocycloalkoxy, and heterocycloalkenyloxy.

In some embodiments, the compounds of the present invention havestructural Formula XIX wherein:

R₁₀ is selected from the group consisting of hydrogen, CN, NO₂, F, Cl,Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.

In other embodiments, the compounds of the present invention havestructural Formula XIX wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted:

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, and heterocycloalkoxy, any of which may be optionallysubstituted; or

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In certain embodiments, the compounds of the present invention havestructural Formula XIX wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ and R₁₀ are hydrogen; and

R₉ is methyl.

In certain embodiments, the compounds of the present invention havestructural Formula XX:

wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted;

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted;

R₆ is selected from the group consisting of perhaloalkyl,S(O)_(m)C(R₇R₈)_(n)CF₃, and C(R₇R₈)_(n)CF₃;

R₇ and R₈ are independently selected from the group consisting ofhydrogen, fluoro, chloro, alkyl, and perhaloalkyl, any of which may beoptionally substituted;

m is an integer between 0 and 2;

n is an integer between 0 and 2; and

with the following provisos when R₆ is trifluoromethyl:

when R₁ is selected from the group consisting of hydroxy, and acetoxy,R₂-R₅ cannot be hydrogen;

when R₁ is hydroxy, R₄ cannot be selected from the group consisting ofCl and Br; and

when R₃ is acetoxy, R₁, R₂, R₄ and R₅ may not be hydrogen.

In some embodiments, the compounds of the present invention havestructural Formula XX:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ are hydrogen; and

R₆ is perfluoroethyl, CF₃CH₂—, and CH₃CF₂—.

In certain embodiments, the compounds of the present invention havestructural Formula XXI:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted.

In other embodiments, the compounds of the present invention havestructural Formula XXI, wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXI, wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XXII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted.

In other embodiments, the compounds of the present invention havestructural Formula XXII, wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXII, wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XXIII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted.

In other embodiments, the compounds of the present invention havestructural Formula XXIII, wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXIII, wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and R₂through R₅ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XXIV:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted.

In other embodiments, the compounds of the present invention havestructural Formula XXIV, wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXIV, wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XXV:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted.

In other embodiments, the invention provides or contemplates a compoundof Formula XXV, wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXV, wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy; and

R₂ through R₅ are hydrogen.

In certain embodiments, the compounds of the present invention havestructural Formula XXVI:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In some embodiments, the compounds of the present invention havestructural Formula XXVI wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXVI wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ are hydrogen; and

R₉ is methyl.

In certain embodiments, the compounds of the present invention havestructural Formula XXVII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In some embodiments, the compounds of the present invention havestructural Formula XXVII wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXVII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ are hydrogen; and

R₉ is methyl.

In certain embodiments, the compounds of the present invention havestructural Formula XXVIII:

wherein:

R₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, cycloalkoxy,cycloalkylalkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted; and

R₉ is selected from the group consisting of hydrogen, alkyl, andperhaloalkyl, any of which may be optionally substituted.

In some embodiments, the compounds of the present invention havestructural Formula XXVIII wherein:

R₁ is chosen from the group consisting of hydroxy, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, and carbamoyloxy, any of whichmay be optionally substituted; and

R₂ through R₅ are, independently, hydrogen, CN, NO₂, F, Cl, Br, alkyl,cycloalkyl, alkoxy, cycloalkoxy, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, cycloalkylsulfonyl, aryl, arylalkyl,aryloxy, arylalkoxy, arylthio, arylalkylthio, heteroaryl,heteroarylalkyl, heteroaryloxy, heteroarylthio, heteroarylalkylthio,heterocycloalkyl, or heterocycloalkoxy, any of which may be optionallysubstituted.

In certain embodiments, the compounds of the present invention havestructural Formula XXVIII wherein:

R₁ is chosen from the group consisting of hydroxy and acetoxy;

R₂ through R₅ are hydrogen; and

R₉ is methyl.

The disclosed compounds include compounds of formula (I), salts, andsolvates thereof. For example, in some embodiments, the compound of thepresent invention may be a salt or a solvate.

Many compounds of this invention are capable of existing in more thanone stereoisomeric form. All depictions of and references to compoundsof this invention are intended to include all diastereomeric andenantiomeric forms of those compounds.

Because compounds of this invention may be used in the diagnosis as wellas the treatment of disease, isotopically labeled versions of thesecompounds are included in this disclosure and in the claims. Allreferences to elements in compounds of this invention are intended toinclude all isotopes of those elements, including unstable isotopes. Forexample, references to “hydrogen” or H in formulas or in claims areintended to include deuterium, (D) and tritium (T.)

In another embodiment, this invention provides or contemplates a kit,comprising, in a compartment, at least one pharmaceutical compositioncomprising, in a pharmaceutically acceptable carrier, an effectiveamount of at least one compound of the invention. In some embodiments,the kit further comprises written instructions for administering thepharmaceutical composition. In some embodiments, written instructionsfor administering concern indications noted elsewhere in thisdisclosure. In some embodiments, written instructions for administeringconcern an administration regimen noted elsewhere in this disclosure.

As used in the present specification the following terms have themeanings indicated:

The term “salts” is used in its broadest sense. For example, the termsalts includes hydrogen salts and hydroxide salts with ions of thepresent compound. In some embodiments, the term salt may be a subclassreferred to as pharmaceutically acceptable salts, which are salts of thepresent compounds having a pharmacological activity and which areneither biologically nor otherwise undesirable. In all embodiments, thesalts can be formed with acids, such as, without limitation, hydrogen,acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate,bisulfate butyrate, citrate, camphorate, camphorsulfonate,cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate,fumarate, glucoheptanoate, glycero-phosphate, hemisulfate, heptanoate,hexanoate, hydrochloride hydrobromide, hydroiodide,2-hydroxyethane-sulfonate, lactate, maleate, methanesulfonate,2-naphthalenesulfonate, nicotinate, oxalate, thiocyanate, tosylate andundecanoate. In all embodiments, the salts can be formed with bases,such as, without limitation, hydroxide, ammonium salts, alkali metalsalts such as lithium, sodium and potassium salts, alkaline earth metalsalts such as calcium, magnesium salts, aluminum salts, salts withorganic bases such as ammonia, methylamine, diethylamine, ethanolamine,dicyclohexylamine, N-methylmorpholine, N-methyl-D-glucamine, and saltswith amino acids such as arginine and lysine. Basic nitrogen-containinggroups can be quarternized with agents including lower alkyl halidessuch as methyl, ethyl, propyl and butyl chlorides, bromides and iodides;dialkyl sulfates such as dimethyl, diethyl, dibutyl and diamyl sulfates;long chain halides such as decyl, lauryl, myristyl and stearylchlorides, bromides and iodides; and aralkyl halides such as benzyl andphenethyl bromides.

The terms “therapeutically acceptable salt,” and “pharmaceuticallyacceptable salt,” as used herein, represent salts or zwitterionic formsof the compounds of the present invention which are water or oil-solubleor dispersible; which are suitable for treatment of diseases withoutundue toxicity, irritation, and allergic-response; which arecommensurate with a reasonable benefit/risk ratio; and which areeffective for their intended use. The salts can be prepared during thefinal isolation and purification of the compounds or separately byreacting the appropriate compound in the form of the free base with asuitable acid. Representative acid addition salts include acetate,adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate(besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate,digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate,glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride,hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate),lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate,methanesulfonate, naphthylenesulfonate, nicotinate,2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate,3-phenylproprionate, phosphonate, picrate, pivalate, propionate,pyroglutamate, succinate, sulfonate, tartrate, L-tartrate,trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate,para-toluenesulfonate (p-tosylate), and undecanoate. Also, basic groupsin the compounds of the present invention can be quaternized withmethyl, ethyl, propyl, and butyl chlorides, bromides, and iodides;dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl,myristyl, and steryl chlorides, bromides, and iodides; and benzyl andphenethyl bromides. Examples of acids which can be employed to formtherapeutically acceptable addition salts include inorganic acids suchas hydrochloric, hydrobromic, sulfuric, and phosphoric, and organicacids such as oxalic, maleic, succinic, and citric. Salts can also beformed by coordination of the compounds with an alkali metal or alkalineearth ion. Hence, the present invention contemplates sodium, potassium,magnesium, and calcium salts of the compounds of the compounds of thepresent invention and the like.

Basic addition salts can be prepared during the final isolation andpurification of the compounds by reacting a carboxy, phenol or similargroup with a suitable base such as the hydroxide, carbonate, orbicarbonate of a metal cation or with ammonia or an organic primary,secondary, or tertiary amine. The cations of therapeutically acceptablesalts include lithium, sodium, potassium, calcium, magnesium, andaluminum, as well as nontoxic quaternary amine cations such as ammonium,tetramethylammonium, tetraethylammonium, methylamine, dimethylamine,trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine,pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine,dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine,1-ephenamine, and N,N-dibenzylethylenediamine. Other representativeorganic amines useful for the formation of base addition salts includeethylenediamine, ethanolamine, diethanolamine, piperidine, andpiperazine.

The term “solvates” is used in its broadest sense. For example, the termsolvates includes hydrates formed when a compound of the presentinvention contains one or more bound water molecules.

The term “acyl,” as used herein, alone or in combination, refers to acarbonyl attached to an alkyl, alkenyl, aryl, heteroaryl, heterocycle,or any other moiety where the atom attached to the carbonyl is carbon.An “acetyl” group refers to a —C(O)CH₃ group. Examples of acyl groupsinclude alkanoyl groups such as formyl, acetyl, and propionyl, aroylgroups such as benzoyl, and mixed alkyl-aryl groups such as cinnamoyl.

The term “acylamino” embraces an amino radical substituted with an acylgroup. An example of an “acylamino” radical is acetylamino (CH₃C(O)NH—)The term “alkenyl,” as used herein, alone or in combination, refers to astraight-chain, branched-chain, or cyclic unsaturated hydrocarbonradical, or a radical containing any combination of straight-chain orbranched-chain, and cyclic moieties, having one or more double bonds andcontaining from 2 to 20 carbon atoms, or, in the case of cyclicmoieties, having from 3 to 20 ring members. In many embodiments alkenylgroups comprise from 2 to 6 carbon atoms. The term “alkenyl groups” isused in its broadest sense. Alkenylene refers to a carbon-carbon doublebond system attached at two or more positions such as ethenylene[(—CH═CH—),(—C::C—)]. For example, the term “(C₂-C₈) alkenyl groups”embraces straight, branched, and cyclic hydrocarbon radicals containing2 to 8 carbon atoms having at least one double bond. Examples ofsuitable alkenyl radicals include ethenyl, also known as vinyl,propenyl, iso-propenyl, butenyl, iso-butenyl, sec-butenyl, tert-butenyl,1,3-butadienyl, n-pentenyl, n-hexenyl, cycloalkenyl radicals such ascyclohexenyl and 1,3-cyclopentadienyl, cycloalkenylalkyl radicals suchas cyclohexenylmethyl, alkenylcycloalkyl radicals such asmethylenecyclohexyl, and the like. The term “alkoxy,” as used herein,alone or in combination, refers to an alkyl ether radical, wherein theterm alkyl is as defined herein. Examples of suitable alkyl etherradicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,iso-butoxy, sec-butoxy, tert-butoxy, cyclopentoxy, and the like.

The term “alkoxyalkoxy,” as used herein, alone or in combination, refersto one or more alkoxy groups attached to the parent molecular moietythrough another alkoxy group. Examples include ethoxyethoxy,methoxypropoxyethoxy, ethoxypentoxyethoxyethoxy and the like.

The term “alkoxyalkyl,” as used herein, alone or in combination, refersto an alkoxy group attached to the parent molecular moiety through analkyl group. The term “alkoxyalkyl” also embraces alkoxyalkyl groupshaving one or more alkoxy groups attached to the alkyl group, that is,to form monoalkoxyalkyl and dialkoxyalkyl groups.

The term “alkoxycarbonyl,” as used herein, alone or in combination,refers to an alkoxy group attached to the parent molecular moietythrough a carbonyl group. Examples of such “alkoxycarbonyl” groupsinclude methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyland hexyloxycarbonyl.

The term “alkoxycarbonylalkyl” embraces radicals having“alkoxycarbonyl,” as defined above substituted to an alkyl radical. Morepreferred alkoxycarbonylalkyl radicals are “lower alkoxycarbonylalkyl”having lower alkoxycarbonyl radicals as defined above attached to one tosix carbon atoms. Examples of such lower alkoxycarbonylalkyl radicalsinclude methoxycarbonylmethyl.

The term “alkyl,” as used herein, alone or in combination, refers to astraight-chain, branched, or cyclic alkyl radical, or a radicalconsisting of any combination of straight, branched, and/or cyclicradicals, which is a saturated aliphatic hydrocarbon group containingfrom 1-20 carbon atoms. In many embodiments, alkyl groups comprise 1-10carbon atoms. In many other embodiments, alkyl groups comprise 1-6carbon atoms. The term “alkyl groups” is used in its broadest sense.Alkyl groups may be optionally substituted as defined herein. Examplesof alkyl radicals include methyl, ethyl, n-propyl, isopropyl,cyclopropyl, cyclopropylmethyl, n-butyl, isobutyl, sec-butyl,tert-butyl, cyclobutyl, pentyl, neopentyl, iso-amyl, hexyl, cyclohexyl,trans-1,2-di-ethylcyclohexyl, octyl, nonyl and the like. For example,the abbreviation “(C₁-C₆)-alkyl groups” includes (C₃-C₆)-cycloalkylgroups as well as straight and branched alkyl groups, and“O(C₁-C₈)-alkyl groups” includes the straight-chain O(C₁-C₈)-alkylgroups, branched O(C₁-C₆″)-alkyl groups, and cyclic O(C₁-C₆)-alkylgroups. The term “alkylene,” as used herein, alone or in combination,refers to a saturated aliphatic group derived from a straight orbranched chain saturated hydrocarbon attached at two or more positions,such as methylene (—CH₂—), ethylene, and 1,3-cyclobutylene.

The term “alkylamino,” as used herein, alone or in combination, refersto an amino group attached to the parent molecular moiety through analkyl group.

The term “alkylaminocarbonyl” as used herein, alone or in combination,refers to an alkylamino group attached to the parent molecular moietythrough a carbonyl group. Examples of such radicals includeN-methylaminocarbonyl and N,N-dimethylcarbonyl.

The term “alkylcarbonyl” and “alkanoyl,” as used herein, alone or incombination, refers to an alkyl group attached to the parent molecularmoiety through a carbonyl group. Examples of such groups includemethylcarbonyl, also known as acetyl; ethylcarbonyl, also known aspropionyl; and 2-methyl-cyclopentylcarbonyl, etc.

The term “alkylidene,” as used herein, alone or in combination, refersto an alkenyl group in which one carbon atom of the carbon-carbon doublebond belongs to the moiety to which the alkenyl group is attached.

The term “alkylsulfinyl,” as used herein, alone or in combination,refers to an alkyl group attached to the parent molecular moiety througha sulfinyl group. Examples of alkylsulfinyl groups includemethylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl.

The term “alkylsulfonyl,” as used herein, alone or in combination,refers to an alkyl group attached to the parent molecular moiety througha sulfonyl group. Examples of alkylsulfinyl groups includemethanesulfonyl, ethanesulfonyl, tert-butanesulfonyl, and the like.

The term “alkylthio,” as used herein, alone or in combination, refers toan alkyl thioether (R—S—) radical wherein the term alkyl is as definedabove. Examples of suitable alkyl thioether radicals include methylthio,ethylthio, n-propylthio, isopropylthio, n-butylthio, iso-butylthio,sec-butylthio, tert-butylthio, ethoxyethylthio, methoxypropoxyethylthio,ethoxypentoxyethoxyethylthio and the like.

The term “alkylthioalkyl” embraces alkylthio radicals attached to analkyl radical. Alkylthioalkyl radicals include “lower alkylthioalkyl”radicals having alkyl radicals of one to six carbon atoms and analkylthio radical as described above. Examples of such radicals includemethylthiomethyl.

The term “alkynyl,” as used herein in its broadest sense, alone or incombination, refers to a straight-chain, branched chain, or cyclicunsaturated hydrocarbon radical, as well as a radical which contains anycombination of straight, branched, and/or cyclic radicals, having one ormore carbon-carbon triple bonds and containing from 2 to 20 carbonatoms. In many embodiments alkynyl groups contain from 2 to 6 carbonatoms. In many other embodiments alkynyl groups contain from 2 to 4carbon atoms. “Alkynylene” refers to a carbon-carbon triple bondattached at two positions such as ethynylene (—C:::C—, —C≡C—). Forexample, (C₂-C₈) alkynyl groups embraces straight, branched, and cyclichydrocarbon chains containing 2 to 8 carbon atoms having at least onetriple bond, and the term includes but is not limited to substituentssuch as ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl,pentyn-1-yl, pentyn-2-yl, 4-methoxypentyn-2-yl, 3-methylbutyn-1-yl,hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl, and thelike, unless otherwise indicated.

The term “amido,” as used herein, alone or in combination, refers to anamino group as described below attached to the parent molecular moietythrough a carbonyl or sulfonyl group. The term “C-amido” as used herein,alone or in combination, refers to a —C(═O)—NR₂ group with R as definedherein. The term “N-amido” as used herein, alone or in combination,refers to a RC(═O)NH— group, with R as defined herein.

The term “amino,” as used herein, alone or in combination, refers to—NRR′, wherein R and R′ are independently selected from the groupconsisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl,alkyl, alkylcarbonyl, aryl, arylalkenyl, arylalkyl, cycloalkyl,haloalkylcarbonyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl,heterocycle, heterocycloalkenyl, and heterocycloalkyl, wherein the aryl,the aryl part of the arylalkenyl, the arylalkyl, the heteroaryl, theheteroaryl part of the heteroarylalkenyl and the heteroarylalkyl, theheterocycle, and the heterocycle part of the heterocycloalkenyl and theheterocycloalkyl can be optionally substituted with one, two, three,four, or five substituents independently selected from the groupconsisting of alkenyl, alkoxy, alkoxyalkyl, alkyl, cyano, halo,haloalkoxy, haloalkyl, hydroxy, hydroxy-alkyl, nitro, and oxo.

The term “aminoalkyl,” as used herein, alone or in combination, refersto an amino group attached to the parent molecular moiety through analkyl group. Examples include aminomethyl, aminoethyl and aminobutyl.The term “alkylamino” denotes amino groups which have been substitutedwith one or two alkyl radicals. Suitable “alkylamino” groups may bemono- or dialkylated, forming groups such as, for example,N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino and thelike.

The terms “aminocarbonyl” and “carbamoyl,” as used herein, alone or incombination, refer to an amino-substituted carbonyl group, wherein theamino group can be a primary or secondary amino group containingsubstituents selected from alkyl, aryl, aralkyl, cycloalkyl,cycloalkylalkyl radicals and the like.

The term “aminocarbonylalkyl,” as used herein, alone or in combination,refers to an aminocarbonyl radical attached to an alkyl radical, asdescribed above. An example of such radicals is aminocarbonylmethyl. Theterm “amidino” denotes an —C(NH)NH₂ radical. The term “cyanoamidino”denotes an —C(N—CN)NH₂ radical.

The term “aralkenyl” or “arylalkenyl,” as used herein, alone or incombination, refers to an aryl group attached to the parent molecularmoiety through an alkenyl group.

The term “aralkoxy” or “arylalkoxy,” as used herein, alone or incombination, refers to an aryl group attached to the parent molecularmoiety through an alkoxy group.

The term “aralkyl” or “arylalkyl,” as used herein, alone or incombination, refers to an aryl group attached to the parent molecularmoiety through an alkyl group.

The term “aralkylamino” or “arylalkylamino,” as used herein, alone or incombination, refers to an arylalkyl group attached to the parentmolecular moiety through a nitrogen atom, wherein the nitrogen atom issubstituted with hydrogen.

The term “aralkylidene” or “arylalkylidene,” as used herein, alone or incombination, refers to an aryl group attached to the parent molecularmoiety through an alkylidene group

The term “aralkylthio” or “arylalkylthio,” as used herein, alone or incombination, refers to an arylalkyl group attached to the parentmolecular moiety through a sulfur atom.

The term “aralkynyl” or “arylalkynyl,” as used herein, alone or incombination, refers to an aryl group attached to the parent molecularmoiety through an alkynyl group.

The term “aralkoxycarbonyl,” as used herein, alone or in combination,refers to a radical of the formula aralkyl-O—C(O)— in which the term“aralkyl,” has the significance given above. Examples of anaralkoxycarbonyl radical are benzyloxycarbonyl (“Z” or “Cbz”) and4-methoxyphenylmethoxycarbonyl (“MOS”).

The term “aralkanoyl,” as used herein, alone or in combination, refersto an acyl radical derived from an aryl-substituted alkanecarboxylicacid such as benzoyl, phenylacetyl, 3-phenylpropionyl (hydrocinnamoyl),4-phenylbutyryl, (2-naphthyl)acetyl, 4-chlorohydrocinnamoyl,4-aminohydrocinnamoyl, 4-methoxyhydrocinnamoyl, and the like. The term“aroyl” refers to an acyl radical derived from an arylcarboxylic acid,“aryl” having the meaning given below. Examples of such aroyl radicalsinclude substituted and unsubstituted benzoyl or napthoyl such asbenzoyl, 4-chlorobenzoyl, 4-carboxybenzoyl,4-(benzyloxycarbonyl)benzoyl, 1-naphthoyl, 2-naphthoyl,6-carboxy-2-naphthoyl, 6-(benzyloxycarbonyl)-2-naphthoyl,3-benzyloxy-2-naphthoyl, 3-hydroxy-2-naphthoyl,3-(benzyloxyformamido)-2-naphthoyl, and the like.

The term “aryl,” as used herein, alone or in combination, means acarbocyclic aromatic system containing one, two or three rings whereinsuch rings may be attached together in a pendent manner or may be fused.The term “aryl” embraces aromatic radicals such as phenyl, naphthyl,anthracenyl, phenanthryl, and biphenyl. The aryl groups of the presentinvention can be optionally substituted with one, two, three, four, orfive substituents independently selected from the groups as definedherein.

The term “arylamino” as used herein, alone or in combination, refers toan aryl group attached to the parent moiety through an amino group, suchas N-phenylamino, and the like.

The terms “arylcarbonyl” and “aroyl,” as used herein, alone or incombination, refer to an aryl group attached to the parent molecularmoiety through a carbonyl group.

The term “aryloxy,” as used herein, alone or in combination, refers toan aryl group attached to the parent molecular moiety through an oxygenatom.

The term “arylsulfonyl,” as used herein, alone or in combination, refersto an aryl group attached to the parent molecular moiety through asulfonyl group.

The term “arylthio,” as used herein, alone or in combination, refers toan aryl group attached to the parent molecular moiety through a sulfuratom.

The terms “carboxy” or “carboxyl,” whether used alone or with otherterms, such as “carboxyalkyl,” denotes —CO₂H.

The terms “benzo” and “benz,” as used herein, alone or in combination,refer to the divalent radical C₆H₄═ derived from benzene. Examplesinclude benzothiophene and benzimidazole.

The term “carbamoyloxy,” as used herein, alone or in combination, refersto an amino-substituted carbonyl group attached to the parent molecularmoiety through a oxygen atom (e.g. RR′NC(═O)O—), wherein the amino groupcan be a primary or secondary amino group containing substituentsselected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl radicalsand the like.

The term “O-carbamyl” as used herein, alone or in combination, refers toa —OC(O)NR, group—with R as defined herein.

The term “C-linked” as used herein, alone or in combination, refers toany substituent that is attached to the parent molecular moiety througha carbon-carbon bond.

The term “N-carbamyl” as used herein, alone or in combination, refers toa ROC(O)NH— group, with R as defined herein.

The term “carbonate” as used herein, alone or in combination, refers toa —O—C(═O)OR group, with R as defined herein.

The term “carbonyl,” as used herein, when alone includes formyl [—C(O)H]and in combination is a —C(O)— group.

The term “carboxy,” as used herein, refers to —C(O)OH or thecorresponding “carboxylate” such as a carboxylic acid salt derivative orester derivative. An “O-carboxy” group refers to a RC(O)O— group, whereR is as defined herein. A “C-carboxy” group refers to a —C(O)OR groupswhere R is as defined herein.

The term “cyano,” as used herein, alone or in combination, refers to—CN.

The term “cycloalkyl,” as used herein, alone or in combination, refersto a saturated or partially saturated monocyclic, bicyclic or tricyclicalkyl radical wherein each cyclic moiety contains from 3 to 12,preferably three to seven, carbon atom ring members and which mayoptionally be a benzo fused ring system which is optionally substitutedas defined herein. Examples of such cycloalkyl radicals includecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,octahydronaphthyl, 2,3-dihydro-1H-indenyl, adamantyl and the like.“Bicyclic” and “tricyclic” as used herein are intended to include bothfused ring systems, such as decahydonapthalene, octahydronapthalene aswell as the multicyclic (multicentered) saturated or partiallyunsaturated type. The latter type of isomer is exemplified in general bybicyclo[2,2,2]octane, bicyclo[2,2,2]octane, bicyclo[1,1,1]pentane,camphor and bicyclo[3,2,1]octane.

The term “cycloalkenyl,” as used herein, alone or in combination, refersto a partially unsaturated monocyclic, bicyclic or tricyclic radicalwherein each cyclic moiety contains from 3 to 12, preferably five toeight, carbon atom ring members and which may optionally be a benzofused ring system which is optionally substituted as defined herein.Examples of such cycloalkenyl radicals include cyclopentenyl,cyclohexenyl, cyclohexadienyl, cycloheptenyl, cyclooctadienyl,-1H-indenyl and the like.

The term “cycloalkylalkyl,” as used herein, alone or in combination,refers to an alkyl radical as defined above which is substituted by acycloalkyl radical as defined above. Examples of such cycloalkylalkylradicals include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl,cyclohexylmethyl, 1-cyclopentylethyl, 1-cyclohexylethyl,2-cyclopentylethyl, 2-cyclohexylethyl, cyclobutylpropyl,cyclopentylpropyl, cyclohexylbutyl and the like.

The term “cycloalkenylalkyl,” as used herein, alone or in combination,refers to an alkyl radical as defined above which is substituted by acycloalkenyl radical as defined above. Examples of suchcycloalkenylalkyl radicals include 1-methylcyclohex-1-enyl-,4-ethylcyclohex-1-enyl-, 1-butylcyclopent-1-enyl-,3-methylcyclopent-1-enyl- and the like.

The term “ester,” as used herein, alone or in combination, refers to acarbonyloxy —(C═O)O— group bridging two moieties linked at carbon atoms.Examples include ethyl benzoate, n-butyl cinnamate, phenyl acetate andthe like.

The term “ether,” as used herein, alone or in combination, refers to anoxy group bridging two moieties linked at carbon atoms.

The term “halo,” or “halogen,” as used herein, alone or in combination,refers to fluorine, chlorine, bromine, or iodine.

The term “haloalkoxy,” as used herein, alone or in combination, refersto a haloalkyl group attached to the parent molecular moiety through anoxygen atom.

The term “haloalkyl,” as used herein, alone or in combination, refers toan alkyl radical having the meaning as defined above wherein one or morehydrogens are replaced with a halogen. Specifically embraced aremonohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkylradical, for one example, may have either an iodo, bromo, chloro orfluoro atom within the radical. Dihalo and polyhaloalkyl radicals mayhave two or more of the same halo atoms or a combination of differenthalo radicals. Examples of haloalkyl radicals include fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, trichloroethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl, difluoroethyl,difluoropropyl, dichloroethyl and dichloropropyl. “Haloalkylene” refersto a halohydrocarbyl group attached at two or more positions. Examplesinclude fluoromethylene (—CFH—), difluoromethylene (—CF₂—),chloromethylene (—CHCl—) and the like. Examples of such haloalkylradicals include chloromethyl, 1-bromoethyl, fluoromethyl,difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, perfluorodecyland the like.

The term “heteroalkyl,” as used herein, alone or in combination, refersto a stable straight or branched chain, or cyclic hydrocarbon radical,or combinations thereof, fully saturated or containing from 1 to 3degrees of unsaturation, consisting of the stated number of carbon atomsand from one to three heteroatoms selected from the group consisting ofO, N, and S, and wherein the nitrogen and sulfur atoms may optionally beoxidized and the nitrogen heteroatom may optionally be quaternized. Theheteroatom(s) O, N and S may be placed at any interior position of theheteroalkyl group. Up to two heteroatoms may be consecutive, such as,for example, —CH₂—NH—OCH₃.

The term “heteroaryl,” as used herein, alone or in combination, refersto an aromatic five- or six-membered ring, where at least one atom isselected from the group consisting of N, O, and S, and the remainingring atoms are carbon. The five-membered rings have two double bonds,and the six-membered rings have three double bonds. The heteroarylgroups are connected to the parent molecular group through asubstitutable carbon or nitrogen atom in the ring. The term “heteroaryl”also includes systems where a heteroaryl ring is fused to an aryl group,as defined herein, a heterocycle group, as defined herein, or anadditional heteroaryl group. Heteroaryls are exemplified bybenzothienyl, benzoxazolyl, benzofuranyl, benzimidazolyl, benzthiazolylbenzotriazolyl, cinnolinyl, furyl, imidazolyl, triazolyl [e.g.,4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.],tetrazolyl [e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc.], indazolyl,indolyl, isoxazolyl, isoquinolinyl, isothiazolyl, naphthyridinyl,oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,5-oxadiazolyl, etc.], oxazolyl, isoxazolyl, purinyl, thiazolyl,isothiazolyl, thienopyridinyl, thienyl, thiadiazolyl [e.g.,1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.],pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl,pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl,quinolinyl, thieno[2,3-c]pyridinyl, tetrazolyl, triazinyl, and the like.The heteroaryl groups of the present invention can be optionallysubstituted with one, two, three, four, or five substituentsindependently selected from the groups as defined herein.

Examples of preferred heteroaryl groups include, without limitation,thienyl, benzothienyl, furyl, benzofuryl, dibenzofuryl, pyrrolyl,imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, indolyl,quinolyl, isoquinolyl, quinoxalinyl, tetrazolyl, oxazolyl, thiazolyl,triazolyl, and isoxazolyl

The term “heteroaralkyl” or “heteroarylalkyl,” as used herein, alone orin combination, refers to a heteroaryl group attached to the parentmolecular moiety through an alkyl group.

The term “heteroaralkenyl” or “heteroarylalkenyl,” as used herein, aloneor in combination, refers to a heteroaryl group attached to the parentmolecular moiety through an alkenyl group.

The term “heteroaralkoxy” or “heteroarylalkoxy,” as used herein, aloneor in combination, refers to a heteroaryl group attached to the parentmolecular moiety through an alkoxy group.

The term “heteroaralkylidene” or “heteroarylalkylidene,” as used herein,alone or in combination, refers to a heteroaryl group attached to theparent molecular moiety through an alkylidene group.

The term “heteroaryloxy,” as used herein, alone or in combination,refers to a heteroaryl group attached to the parent molecular moietythrough an oxygen atom.

The term “heteroarylsulfonyl,” as used herein, alone or in combination,refers to a heteroaryl group attached to the parent molecular moietythrough a sulfonyl group.

The terms “heterocycloalkyl” and, interchangeably, “heterocycle,” asused herein, alone or in combination, each refer to a saturated,partially unsaturated, or fully unsaturated monocyclic, bicyclic, ortricyclic heterocyclic radical containing one or more heteroatoms asring members, wherein each said heteroatom may be independently selectedfrom the group consisting of nitrogen, oxygen, and sulfur, and whereinthere are typically 3 to 8 ring members in each ring. Most commonlyheterocyclic rings contain 5 to 6 ring members. In some embodiments ofthis invention heterocyclic rings contain 1 to 4 heteroatoms; in otherembodiments, heterocyclic rings contain 1 to 2 heteroatoms.“Heterocycloalkyl” and “heterocycle” are intended to include sulfones,sulfoxides, N-oxides of tertiary nitrogen ring members, and carbocyclicfused and benzo fused ring systems; additionally, both terms alsoinclude systems where a heterocycle ring is fused to an aryl group, asdefined herein, or an additional heterocycle group. Heterocycle groupsof the invention are exemplified by aziridinyl, azetidinyl,1,3-benzodioxolyl, dihydroisoindolyl, dihydroisoquinolinyl,dihydrocinnolinyl, dihydrobenzodioxinyl,dihydro[1,3]oxazolo[4,5-b]pyridinyl, benzothiazolyl, dihydroindolyl,dihy-dropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl,isoindolinyl, morpholinyl, piperazinyl, pyrrolidinyl,tetrahydropyridinyl, piperidinyl, thiomorpholinyl, and the like. Theheterocycle groups may be optionally substituted unless specificallyprohibited.

The term “heterocycloalkenyl,” as used herein, alone or in combination,refers to a heterocycle group attached to the parent molecular moietythrough an alkenyl group.

The term “heterocycloalkoxy,” as used herein, alone or in combination,refers to a heterocycle group attached to the parent molecular groupthrough an oxygen atom.

The term “heterocycloalkylalkyl,” as used herein, alone or incombination, refers to an alkyl radical as defined above in which atleast one hydrogen atom is replaced by a heterocycloalkyl radical asdefined above, such as pyrrolidinylmethyl, tetrahydrothienylmethyl,pyridylmethyl and the like.

The term “heterocycloalkylidene,” as used herein, alone or incombination, refers to a heterocycle group attached to the parentmolecular moiety through an alkylidene group.

The term “hydrazinyl” as used herein, alone or in combination, refers totwo amino groups joined by a single bond, i.e., —N—N—.

The term “hydroxy,” as used herein, alone or in combination, refers to—OH.

The term “hydroxyalkyl” as used herein, alone or in combination, refersto a linear or branched alkyl group having one to about ten carbon atomsany one of which may be substituted with one or more hydroxyl radicals.Examples of such radicals include hydroxymethyl, hydroxyethyl,hydroxypropyl, hydroxybutyl and hydroxyhexyl.

The term “hydroxyalkyl,” as used herein, alone or in combination, refersto a hydroxy group attached to the parent molecular moiety through analkyl group.

The term “imino,” as used herein, alone or in combination, refers to═N—.

The term “iminohydroxy,” as used herein, alone or in combination, refersto ═N(OH) and ═N—O—.

The phrase “in the main chain” refers to the longest contiguous oradjacent chain of carbon atoms starting at the point of attachment of agroup to the compounds of this invention.

The term “isocyanato” refers to a —NCO group.

The term “isothiocyanato” refers to a —NCS group.

The phrase “linear chain of atoms” refers to the longest straight chainof atoms independently selected from carbon, nitrogen, oxygen andsulfur.

The term “lower,” as used herein in such terms as “lower alkyl,” aloneor in combination, means containing from 1 to and including 6 carbonatoms.

The term “mercaptoalkyl” as used herein, alone or in combination, refersto an R′SR— group, where R and R′ are as defined herein.

The term “mercaptomercaptyl” as used herein, alone or in combination,refers to a RSR′S— group, where R is as defined herein.

The term “mercaptyl” as used herein, alone or in combination, refers toan RS— group, where R is as defined herein.

The term “null” refers to a lone electron pair.

The term “nitro,” as used herein, alone or in combination, refers to—NO₂.

The term “optionally substituted” means the anteceding group may besubstituted or unsubstituted. When substituted, the hydrogen atoms boundto the carbon, nitrogen, sulfur, or oxygen atoms are replaced by“substituents” which may include carbonyl (oxo), carboxyl, lower alkylcarboxylate, lower alkyl carbonate, lower alkyl carbamate, halogen,hydroxy, amino, amido, cyano, hydrazinyl, hydrazinylcarbonyl,alkylhydrazinyl, dialkylhydrazinyl, arylhydrazinyl,heteroarylhydrazinyl, nitro, thiol, sulfonic acid, trisubstituted silyl,urea, acyl, acyloxy, acylamino, acylthio, lower alkyl, lower alkylamino,lower dialkylamino, lower alkyloxy, lower alkoxyalkyl, lower alkylthio,lower alkylsulfonyl, lower alkenyl, lower alkenylamino, lowerdialkenylamino, lower alkenyloxy, lower alkenylthio, lower alkenylsulfonyl, lower alkynyl, lower alkynylamino, lower dialkynylamino, loweralkynyloxy, lower alkynylthio, lower alkynylsulfonyl, lower cycloalkyl,lower cycloalkyloxy, lower cycloalkylamino, lower cycloalkylthio, lowercycloalkylsulfonyl, lower cycloalkylalkyl, lower cycloalkylalkyloxy,lower cycloalkylalkylamino, lower cycloalkylalkylthio, lowercycloalkylalkylsulfonyl, aryl, aryloxy, arylamino, arylthio,arylsulfonyl, arylalkyl, arylalkyloxy, arylalkylamino, arylalkylthio,arylalkylsulfonyl, heteroaryl, heteroaryloxy, heteroarylamino,heteroarylthio, heteroarylsulfonyl, heteroarylalkyl, heteroarylalkyloxy,heteroarylalkylamino, heteroarylalkylthio, heteroarylalkylsulfonyl,heterocycloalkyl, heterocycloalkyloxy, heterocycloalkylamino,heterocycloalkylthio, heterocycloalkylsulfonyl, lower haloalkyl, lowerhaloalkenyl, lower haloalkynyl, lower perhaloalkyl, lower perhaloalkoxy,lower haloalkoxy, and lower acyloxy. Two substituents may be joinedtogether to form a fused four-, five-, six-, or seven-memberedcarbocyclic or heterocyclic ring consisting of zero to threeheteroatoms, for example forming methylenedioxy or ethylenedioxy. Anoptionally substituted group may be unsubstituted (e.g., —CH₂CH₃), fullysubstituted (e.g., —CF₂CF₃), monosubstituted (e.g., —CH₂CH₂F) orsubstituted at a level anywhere in-between fully substituted andmonosubstituted (e.g., —CH₂CF₃). Where substituents are recited withoutqualification as to substitution, both substituted and unsubstitutedforms are encompassed. Where a substituent is qualified as“substituted,” the substituted form is specifically intended. Allpendant aryl, heteroaryl, and heterocyclo moieties can be furtheroptionally substituted with one, two, three, four, or five substituentsindependently selected from the groups listed above.

The terms “oxy” or “oxa,” as used herein, alone or in combination, referto —O—.

The term “oxo” as used herein, alone or in combination, refers to adoubly bonded oxygen ═O.

The term “perhaloalkoxy” refers to an alkoxy group where all of thehydrogen atoms are replaced by halogen atoms.

The term “perhaloalkyl” as used herein, alone or in combination, refersto an alkyl group where all of the hydrogen atoms are replaced byhalogen atoms.

The term “phosphonate” as used herein, alone or in combination, refersto the —P(═O)(OG)(OG1) group, where G and G1 are chosen from H, alkyl,alkenyl, alkynyl, aryl, heteroaryl, etc.

The term “phosphinate” as used herein, alone or in combination, refersto the —P(═O)(G)(OG1) group, where G and G1 are chosen from H, alkyl,alkenyl, alkynyl, aryl, heteroaryl, etc.

The terms “sulfonate,” “sulfonic acid,” and “sulfonic,” as used herein,alone or in combination, refer the —SO₃H group and its anion as thesulfonic acid is used in salt formation.

The term “sulfanyl,” as used herein, alone or in combination, refers to—S and —S—.

The term “sulfinyl,” as used herein, alone or in combination, refers to—S(O)—.

The term “sulfonyl,” as used herein, alone or in combination, refers to—SO₂—.

The term “N-sulfonamido” refers to a RS(═O)₂NH— group with R as definedherein.

The term “S-sulfonamido” refers to a —S(═O)₂NR₂, group, with R asdefined herein.

The terms “thia” and “thio,” as used herein, alone or in combination,refer to a —S— group or an ether wherein the oxygen is replaced withsulfur. The oxidized derivatives of the thio group, namely sulfinyl andsulfonyl, are included in the definition of thia and thio.

The term “thioether,” as used herein, alone or in combination, refers toa thio group bridging two moieties linked at carbon atoms.

The term “thiol,” as used herein, alone or in combination, refers to an—SH group.

The term “thiocarbonyl,” as used herein, when alone includes thioformyl—C(S)H and in combination is a —C(S)— group.

The term “N-thiocarbamyl” refers to an ROC(S)NH— group, with R asdefined herein.

The term “O-thiocarbamyl” refers to a —OC(S)NR, group with R as definedherein.

The term “thiocyanato” refers to a —CNS group.

The term “trihalomethanesulfonamido” refers to a X₃CS(O)₂NR— group withX is a halogen and R as defined herein.

The term “trihalomethanesulfonyl” refers to a X₃CS(O)₂— group where X isa halogen.

The term “trihalomethoxy” refers to a X₃CO— group where X is a halogen.

The term “trisubstituted silyl,” as used herein, alone or incombination, refers to a silicone group substituted at its three freevalences with groups as listed herein under the definition ofsubstituted amino. Examples include trimethysilyl,tert-butyldimethylsilyl, triphenylsilyl and the like.

The term “urea,” as used herein, alone or in combination, refers to—N(R)C(═O)N(R)(R), with R as defined herein.

The term “carrier” is used in its broadest sense. For example, the termcarrier refers to any carriers, diluents, excipients, wetting agents,buffering agents, suspending agents, lubricating agents, adjuvants,vehicles, delivery systems, emulsifiers, disintegrants, absorbents,preservatives, surfactants, colorants, flavorants, and sweeteners. Insome embodiments, the carrier may be a pharmaceutically acceptablecarrier, a term narrower than carrier, because the term pharmaceuticallyacceptable carrier” means a non-toxic that would be suitable for use ina pharmaceutical composition.

The present invention also relates to a pharmaceutical compositioncomprising, in a pharmaceutically acceptable carrier, an effectiveamount of at least one compound of the invention.

The term effective amount is used in its broadest sense. The term, forexample, refers to the amount required to produce a desired effect.

In some embodiments, the compound of the invention is present in apharmaceutical composition in an effective amount for treating HCVinfection (e.g., chronic HCV infection). “Treating HCV infection” mayrefers to: (i) preventing HCV infection from occurring in an animal thatmay be predisposed to HCV infection but has not yet been diagnosed ashaving it; (ii) inhibiting or slowing HCV infection, e.g. arresting itsdevelopment; (iii) relieving chronic infection, e.g. causing itsregression; (iv) improving a symptom in a subject having chronicinfection; and/or (v) prolonging the survival of a subject havingchronic infection.

In any embodiment of the compounds of formula (I), R₁ through R₅ may bethe same, may be different, or some members of R₁ through R₅ may be thesame while the others are different. Any combination is possible.

Examples of compounds of the present invention may include, but are notlimited to the following compounds listed in Table 1 below:

TABLE 1 No. Structure 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

Table 2 designates the melting points of various compounds.

TABLE 2 Melting No. Structure Point (° C.) 1

127.5-129.0 2

260-264 (dec) 3

126-128 4

254-257 5

172-174 6

>300

For the above compounds that have a trifluoromethyl group (—CF₃), it isalso envisioned by the inventors that in place of the trifluoromethyl, amoiety selected from —CF₂H, —CH₂CF₃, —CF₂CH₃, —CF₂CF₃, —SCF₃, —SO₂CF₃,—OCF₃ and —CH₂CH₂CF₃ may be used.

Compounds of Formula (I), where R₆ is any of haloalkyl, perhaloalkyl,haloalkoxy, perhaloalkoxy, S(O)_(m)C(R₇R₈)_(n)CF₃, and C(R₇R₈)_(n)CF₃,may be synthesized by reacting an aroyl derivative, wherein G₁ ishydroxy, chloro, fluoro, bromo, alkoxy and the like with aheteroaromatic amine as shown below, wherein W, X, and Y are as definedabove, under suitable reaction conditions. In some embodiments, thereaction may be generically represented as follows:

Examples of the invention, compounds (1) and (2), may be synthesized bythe method described in the following reaction scheme.2-Amino-5-trifluoromethyl-thiazole was prepared by a modification of theprocedure of Laduron et al. J. Fluorine Chem. 1995, 73, 83-86. Couplingof o-acetylsalicyloyl chloride and 2-Amino-5-trifluoromethylthiazole inthe presence of a suitable base, including tertiary amines liketriethylamine, in a suitable inert solvent like dichloromethane, atabout 0° C. to about ambient room temperature, affords compound (1).Hydrolysis of the acetyl moiety of compound (1) with dilute hydrochoricacid at room temperature to about 50° C. yields compound (2).

Further examples of the invention, compounds (3) and (4), may besynthesized via the synthetic pathway outlined in the scheme below,using commercially available 2-amino-4-trifluoromethylthiazole as astarting material.

The compositions of the present invention may be formulated as solid orliquid dosage forms, or as pastes or ointments, and may optionallycontain further active ingredients.

A pharmaceutical composition of the present invention comprises apharmaceutically acceptable carrier, which is not particularly limited,and includes a wide range of carriers known to those of ordinary skillin the art, and including wetting or dispersing agents, starchderivatives, excipients, and the like. Tablet embodiments may optionallycomprise a coating of a substance that constitutes an enteric coating,i.e., a coating that substantially insoluble in gastric secretion butsubstantially soluble in intestinal fluids.

Pharmaceutical compositions comprising the compounds of the presentinvention are in some embodiments formulated for oral administration andare optionally in the form of a liquid, for example an emulsion or asolution or a suspension in water or oil such as arachis oil, or otherliquid. Formulations of non-aqueous micellar solutions may be preparedaccording to the method disclosed in U.S. Pat. No. 5,169,846.Alternatively, tablets can be manufactured, for example, by performingthe following steps: wet granulation; drying; and compression. Filmcoating may generally be performed with organic solvents.

The present invention is a method, comprising administering to a subjectat least one compound of the present invention in an amount in aneffective amount for treating HCV infection (e.g., chronic HCVinfection). In some embodiments, the method, comprising administering toa subject at least one pharmaceutical composition which comprises atleast one compound of the present invention in an amount in an effectiveamount for treating HCV infection (e.g., chronic HCV infection).

In some embodiments, the subject is chosen from animals. In someembodiments, the subject is chosen from mammals. In some embodiments,the subject is chosen from pets, such as mice, dogs, cats, etc. In someembodiments, the subject is chosen from humans.

In some embodiments, the invention provides a method of treating a viralinfection in a subject, comprising administering to the subject at leastone dose of an effective amount of at least one compound of the presentinvention. In some embodiments, the invention provides a method oftreating a viral infection in a subject, comprising administering to thesubject at least one dose of an effective amount of at least onepharmaceutical composition comprising, in a pharmaceutically acceptablecarrier, at least one compound of the present invention.

In some embodiments the antiviral treatment or prophylactic dosages ofthe compound of the present invention may depend upon the weight of thesubject, and may be inferred by one of ordinary skill without undueexperimentation by reference to the following examples, which are setforth for purposes of illustration and are not intended to be limiting.

The inventive compounds and compositions may be administered locally orsystemically by any means known to an ordinarily skilled artisan. Forexample, the inventive compounds and compositions may be administeredorally, parenterally, by inhalation spray, topically, rectally, nasally,buccally, vaginally or via an implanted reservoir in dosage formulationscontaining conventional non-toxic pharmaceutically acceptable carriers,adjuvants and vehicles. The term parenteral as used herein includessubcutaneous, intravenous, intraarterial, intramuscular,intraperitoneal, intrathecal, intraventricular, intrasternal,intracranial or intraosseous injection and infusion techniques. Theexact administration protocol will vary depending upon various factorsincluding the age, body weight, general health, sex and diet of thepatient; the determination of specific administration procedures wouldbe routine to an ordinarily skilled artisan.

Dose levels on the order of about 0.1 to about 100 mg/kg of the activeingredient compound are useful in the treatment of the above conditions(e.g., 0.1 mg/kg-day). In some embodiments, the amounts range from about1 to about 10 mg/kg, and in other embodiments, the amounts range fromabout 2 to about 5 mg/kg. The specific dose level for any particularpatient will vary depending upon a variety of factors, including theactivity and the possible toxicity of the specific compound employed;the age, body weight, general health, sex and diet of the patient; thetime of administration; the rate of excretion; drug combination; theseverity of the particular disease being treated; and the form ofadministration. Typically, in vitro dosage-effect results provide usefulguidance on the proper doses for patient administration. Studies inanimal models are also helpful. The considerations for determining theproper dose levels are well known in the art.

Any administration regimen for regulating the timing and sequence ofdrug delivery can be used and repeated as necessary to effect treatment.Such regimen may include multiple uses or preadministration and/orco-administration and/or postadministration with food, liquid, or water.

As noted above, this invention provides or contemplates a kit,comprising at least one compound of the invention. The kit could takeany form. By way of example, a kit includes one or more containers forstoring a pharmaceutical composition. In some embodiments, a containercontains written instructions for administering the pharmaceuticalcomposition. In some embodiments, a container contains is the substratefor the written instructions for administering the pharmaceuticalcomposition. In some embodiments, the written instructions foradministering the pharmaceutical composition are affixed to a container,for example, as in a container for filling a prescription sometimes haswritten instructions affixed on a surface.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andits examples be considered as exemplary only, with a true scope andspirit of the invention being indicated by what may eventually beclaimed.

EXAMPLES

1. Materials and Methods

1.1 Materials.

All test compounds were provided by Romark Laboratories, Nitazoxanideand Tizoxanide were used as standards.

1.2. HBV studies.

1.2.1. Antiviral Assays.

HBV antiviral assays were conducted as previous described [Korba andGerin, Antiviral Res. 19:55 (1992 Confluent cultures of 2.2.15 cellswere maintained on 96-well flat-bottomed tissue culture plates(confluence in this culture system is required for active, high levelsof HBV replication equivalent to that observed in chronically-infectedindividuals [Sells et al. J. Virol. 62, 2836-2844 (1988); Korba andGerin (1992)]. Cultures were treated with nine consecutive daily dosesof the test compounds. HBV DNA levels were assessed by quantitative blothybridization 24 hr. after the last treatment. Cytotoxicity was assessedby uptake of neutral red dye 24 hr. following the last treatment.

1.2.3. Production of HBV Proteins.

Cultures of 2.2.15 cells were treated under standard procedures andsemi-quantitative EIA-based analysis of HBV proteins was performed aspreviously described [Korba and Gerin, Antivir. Res. 28, 225-242(1995)], except that HBeAg was analyzed ETI-EBK Plus®(DiaSorin, Inc.,Stillwater, Minn. USA). Samples were diluted (2 to 10-fold) to bringlevels into the dynamic response ranges of the EIA's. HBsAg, and HBeAgwere analyzed from culture medium samples and HBcAg was analyzed fromintracellular lysates. Intracellular HBV RNA was assessed byquantitative northern blot hybridization (Korba and Gerin, 1995).

1.3. HCV Studies.

Antiviral activity of test compounds was assessed in a 3-day assay usingthe stably-expressing HCV replicon cell line, AVA5 (sub-genomic CONI,genotype 1b) [Blight et al., Science 290, 1972-1974 (2000)] maintainedas sub-confluent cultures on 96-well plates as previously described(Okuse et al., Antiviral Research 65, 23-34 (2005)]. Antiviral activitywas determined by blot hybridization analysis of intracellular HCV RNA(normalized to the level of cellular B-actin RNA in each culture sample)and cytotoxicity was assessed by neutral red dye uptake after 3 days oftreatment. Additional studies were performed using Huh7 cells containinganother HCV replicon, H/FL-Neo, a genotype 1a full length construct[Blight et al., J. Virol. 77, 3181-3190 (2003)]. For studies involvinghuman serum, standard culture medium (which contains 10% fetal bovineserum) and assay conditions were maintained.

1.4. Presentation of Results.

EC₅₀, EC₉₀ and CC₅₀ values (±standard deviations [S.D.]) were calculatedby linear regression analysis using data combined from all treatedcultures (Korba and Gerin, 1992; Okuse et al., 2005). EC₅₀ and EC₉₀ aredrug concentrations at which a 2-fold, or a 10-fold depression ofintracellular HBV DNA or HCV RNA (relative to the average levels inuntreated cultures), respectively, was observed. CC₅₀ is the drugconcentration at which a 2-fold lower level of neutral red dye uptake(relative to the average levels in untreated cultures) was observed.Selectivity index (S.I.) was calculated as CC₅₀/EC₉₀ for HBV assays andCC₅₀/EC₅₀ for HCV assays. EC₉₀ values were used for calculation of theS.I. in HBV assays since at least a 3-fold depression of HBV DNA levelsis typically required to achieve statistical significance in this assaysystem (Korba and Gerin, 1992). For combination treatments, EC₅₀, EC₉₀,CC₅₀ and S.I. are presented for the first compound listed. The molarratio of the compounds in each combination is also indicated.

2. Results

TABLE 3 HBV Extracellular Virion Assay Results. EC₅₀ EC₉₀ CC₅₀ (VIR)(VIR) SI Compd # (μM) (μM) (μM) (VIR) Nitazoxanide > 100.0 A C > 121(reference) Tizoxanide > 100.0 A C > 172 (reference) 1 > 100.0 D E > 112 > 100.0 D E > 11 3 > 100.0 > E > E 4 > 100.0 > E > E 5 > 100.0 > E > E6 > 100.0 > E > E Legend: A: 0.05-0.2; B: 0.2-0.8; C: 0.8-3.2; D:3.2-4.0; E: >4.0

Nitazoxanide (reference)

Tizoxanide (reference)

Table 4 presents data from the primary HCV replicon cell assay.

TABLE 4 Primary HCV Replicon Cell Assay. PRIMARY ASSAY, GENOTYPE 1B CC50EC50 EC90 Compound (μM) (μM) (μM) SI Nitazoxanide (reference) 32.0 B C169.0 Tizoxanide (reference) 15.0 B C 100.0 1 3.7 D E 0.9 2 0.46 A A58.0 3 in test 4 in test 5 15.0 D E 15.0 6 5.3 D E 1.4 EC50 & EC90Legand A: 0.005-0.05; B: 0.05-0.5; C: 0.5-10; D: 0-5.0; E: >5.0

TABLE 5 Antiviral Activity of Thiazolides Against Paramyxovirus,Influenza A and Coronavirus in Cell Assays Paramyxovirus (Sendai virus)-Influenza A (PR8)- Coronavirus (CCoV)- 37RC cells MDCK cells A72 cellsToxicity Toxicity Toxicity Virus Yield LD₅₀ S.I. Virus Yield LD₅₀ S.I.Virus Yield LD₅₀ S.I. ID₅₀ ID₉₀ (MTT) LD₅₀/ ID₅₀ ID₉₀ (MTT) LD₅₀/ ID₅₀ID₉₀ (MTT) LD₅₀/ Compound RM# μg/ml μg/ml μg/ml ID₅₀ μg/ml μg/ml μg/mlID₅₀ μg/ml μg/ml μg/ml ID₅₀ Nitazoxanide NTZ 1 6 >50 >50 1 7 >50 >50(reference) Tizoxanide TIZ 0.5 5 >50 >100 1 9 >50 >50 1 1.5 >50 >50(reference) 1 RM5036 2 RM5037 3 RM5034 4 RM5035 5 RM4816 3 9 >50 >17 39 >50 >16.7 6 RM5033

TABLE 6 Antiviral Activity of Thiazolides Against Rhinovirus,Respiratory Syncytial Virus and Herpesvirus in Cell Assays Rhinovirus(RHV-2) Respiratory Syncytial Herpesvirus (HSV-1)- HeLa R19 cells Virus(RV-A2)-HeLa cells Hep-2 cells Toxicity Toxicity Virus Toxicity VirusYield LD₅₀ S.I. Virus Yield LD₅₀ S.I. Yield LD₅₀ S.I. ID₅₀ ID₉₀ (MTT)LD₅₀/ ID₅₀ ID₉₀ (MTT) LD₅₀/ ID₅₀ ID₉₀ (MTT) LD₅₀/ Compound RM# μg/mlμg/ml μg/ml ID₅₀ μg/ml μg/ml μg/ml ID₅₀ μg/ml μg/ml μg/ml ID₅₀Nitazoxanide NTZ 2.5 >50 >50 >20 0.025 0.5 >50 >2000 (reference)Tizoxanide TIZ 0.3 40 >50 >167 0.5 — 3 6 2 5 50 25 (reference) 1 RM50369 >50 >50 >5.5 0.2 2 >50 >250 2 RM5037 3 RM5034 0.03 1.5 >50 >1667 4RM5035 0.15 1.5 >50 >333 5 RM4816 6 RM5033 0.2 1 >50 >250

TABLE 7 Antiviral Activity of Thiazolides Against Rotavirus (2 strains)and Adenovirus in Cell Assays Rotavirus (Simian SA11)- Rotavirus(WAG8P1)- Adenovirus (Ad5)- MA104 cells MA104 cells HeLa R19 cellsToxicity Toxicity Toxicity Virus Yield LD₅₀ S.I. Virus Yield LD₅₀ S.I.Virus Yield LD₅₀ S.I. ID₅₀ ID₉₀ (MTT) LD₅₀/ ID₅₀ ID₉₀ (MTT) LD₅₀/ ID₅₀ID₉₀ (MTT) LD₅₀/ Compound RM# μg/ml μg/ml μg/ml ID₅₀ μg/ml μg/ml μg/mlID₅₀ μg/ml μg/ml μg/ml ID₅₀ Nitazoxanide NTZ 1 10 >50 >50 10 40 >50 >51.5 15 >50 >33.3 (reference) Tizoxanide TIZ 0.5 4 >50 >100 1 15 >50 >500.2 0.3 0.8 5 (reference) 1 RM5036 0.1 3.5 4 40 2 RM5037 3 RM5034 4RM5035 5 RM4816 6 RM5033

TABLE 8 Antiviral Activity of thiazolides Against Rhabdovirus in CellAssays Rhabdovirus (VSV)-MA104 cells Toxicity Virus Yield LD₅₀ ID₅₀ ID₉₀(MTT) S.I. Compound RM # μg/ml μg/ml μg/ml LD₅₀/ID₅₀ Nitazoxanide NTZ(reference) Tizoxanide TIZ 2 15 50 25 (reference) 1 RM5036 2 RM5037 3RM5034 4 RM5035 5 RM4816 6 RM5033

The invention claimed is:
 1. A pharmaceutical composition comprising acompound of Formula I:

wherein: R₁ through R₅ and R₁₀ are, independently, hydrogen, CN, NO₂, F,Cl, Br, I, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenyl,cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, alkoxy,alkenyloxy, alkynyloxy, alkoxyalkyl, alkoxyalkenyl, alkoxyalkynyl,alkenyloxyalkyl, alkenyloxyalkenyl, alkenyloxyalkynyl, alkynyloxyalkyl,alkenyloxyalkenyl, alkenyloxyalkynyl, cycloalkoxy, cycloalkylalkoxy,cycloalkylalkenyloxy, cycloalkylalkynyloxy, cycloalkenyloxy,cycloalkenylalkoxy, cycloalkenylalkenyloxy, cycloalkenylalkynyloxy,alkoxyalkylamino, hydroxyalkyl, acyl, acyloxy, aroyloxy,arylalkanoyloxy, arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyl, aryloxycarbonyl,arylalkoxycarbonyl, heteroaryloxycarbonyl, heteroarylalkoxycarbonyl,alkoxycarbonyloxy, carbamoyl, carbamoyloxy, alkylamino, dialkylamino,alkylaminoalkyl, amido, alkylamido, dialkylamido, haloalkyl,perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl,alkylsulfonylalkyl, alkenylsulfonyl, alkynylsulfonyl,cycloalkylsulfonyl, cycloalkylalkylsulfonyl, cycloalkylsulfonylalkyl,cycloalkylalkylsulfonylalkyl, arylsulfonyl, arylalkylsulfonyl,arylalkenylsulfonyl, heteroarylsulfonyl, heteroarylalkylsulfonyl,heteroarylalkenylsulfonyl, alkylsulfonamido, N,N′-dialkylsulfonamido,sulfonamidoalkyl, sulfonamidoaryl, sulfonamidoarylalkyl,sulfonamidoarylalkenyl, aryl, arylalkyl, aryloxy, arylalkoxy, arylthio,arylalkylthio, arylamino, arylalkylamino, arylalkenyl, arylalkynyl,heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl,heteroaryloxy, heteroarylalkoxy, heteroarylamino, heteroarylalkylamino,heteroarylthio, heteroarylalkylthio, heteroarylalkylamino,heterocycloalkyl, heterocycloalkenyl, heterocycloalkoxy, orheterocycloalkenyloxy, any of which may be optionally substitutedwherein R₆ is selected from the group consisting of haloalkyl,perhaloalkyl, haloalkoxy, perhaloalkoxy, S(O)_(m)C(R₇R₈)_(n)CF₃, andC(R₇R₈)_(n)CF₃; wherein W, X and Y are, independently, S, O, N, NR₉ orCR₁₀ where at least two of W, X, and Y are S, O, N, or NR₉; wherein R₇,R₈, and R₉ are, independently, hydrogen, fluoro, chloro, alkyl,perhaloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, ortogether with the atoms to which they are attached, may be joined toform an optionally substituted 4-to 8-membered heterocycloalkyl or anoptionally substituted 3- to 8-membered cycloalkyl ring, any of whichmay be optionally substituted; m is an integer between 0 and 2; and n isan integer between 0 and 5; or a pharmaceutically acceptable salt orester thereof, and a pharmaceutically acceptable carrier, wherein thecomposition comprises an effective amount of the compound for treating aviral pathogen.
 2. The pharmaceutical composition of claim 1, whereinthe viral pathogen is Hepatitis B or Hepatitis C Virus infection.
 3. Thepharmaceutical composition of claim 1, wherein the viral pathogen is aparainfluenza, an influenza A, or an influenza B infection.
 4. A methodfor treating a viral infection comprising administering thepharmaceutical composition of claim 1 to a patient in need thereof.
 5. Amethod for treating a viral infection comprising administering thepharmaceutical composition as claimed in claim 1, to a patient in needthereof, in combination with another antiviral composition.
 6. Themethod of claim 4, wherein the viral infection is selected from thegroup consisting of respiratory viruses, herpes viruses, andgastrointestinal viruses.
 7. The method of claim 6, wherein saidrespiratory viral infection is selected from the group consisting ofparainfluenza, influenza A, influenza B, coronavirus, rhinovirus (RHV),and respiratory syncytial virus (RSV).
 8. The method of claim 6, whereinsaid gastrointestinal virus is selected from the group consisting ofrotavirus and adenovirus.
 9. A method for treating rhabdoviruscomprising administering the pharmaceutical composition of claim 1 to apatient in need thereof.
 10. The pharmaceutical composition of claim 1,wherein: R₁ through R₅ and R₁₀ are, independently, hydrogen, cyano,nitro, halo, hydroxy. alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy,alkynyloxy, acyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl,aryloxycarbonyl, heteroaryloxycarbonyl, alkoxycarbonyloxy, carbamoyl,carbamoyloxy, alkylamino, haloalkyl, perhaloalkyl, perhaloalkoxy,alkylthio, perhaloalkylthio, alkylthioalkyl, alkylsulfonyl,alkylsulfonylalkyl, arylsulfonyl, heteroarylsulfonyl, alkylsulfonamido,sulfonamidoalkyl, aryl, aryloxy, arylalkoxy, arylthio, arylalkylthio,arylamino, arylalkylamino, heteroaryl, heteroarylalkyl, heteroaryloxy,heteroarylalkoxy, heteroarylamino, heteroarylalkylamino, heteroarylthio,heteroarylalkylthio, heterocycloalkyl, and heterocycloalkoxy, alloptionally substituted with substituents selected independently fromcarbonyl (oxo), carboxyl, lower alkyl carboxylate, lower alkylcarbonate, lower alkyl carbamate, halogen, hydroxy, amino, amido, cyano,hydrazinyl, hydrazinylcarbonyl, alkylhydrazinyl, dialkylhydrazinyl,arylhydrazinyl, heteroarylhydrazinyl, nitro, thiol, sulfonic acid,trisubstituted silyl, urea, acyl, acyloxy, acylamino, arylthio, loweralkyl, lower alkylamino, lower dialkylamino, lower alkyloxy, loweralkoxyalkyl, lower alkylthio, lower alkylsulfonyl, lower alkenyl, loweralkenylamino, lower dialkenylamino, lower alkenyloxy, lower alkenylthio,lower alkenyl sulfonyl, lower alkynyl, lower alkynylamino, lowerdialkynylamino, lower alkynyloxy, lower alkynylthio, loweralkynylsulfonyl, lower cycioalkyl, lower cycioalkyloxy, lowercycioalkylamino, lower cycloalkylthio, lower cycioalkylsulfonyl, lowercycioalkylalkyl, lower cycioalkylalkyloxy, lower cycioalkylalkylamino,lower cycioalkylalkylthio, lower cycioalkylalkylsulfonyl, aryl, aryloxy,arylamino, arylthio, arylsulfonyl, arylalkyl, arylalkyloxy,arylalkylamino, arylalkylthio, arylalkylsulfonyl, heteroaryl,heteroaryloxy, heteroarylamino, heteroarylthio, heteroarylsulfonyl,heteroarylalkyl, heteroarylalkyloxy, heteroarylalkylamino,heteroarylalkylthio, heteroarylalkylsulfonyl, heterocycioalkyl,heterocycioalkyloxy, heterocycioalkylamino, heterocycioalkylthio,heterocycloalkylsulfonyl, lower haloalkyl, lower haloalkenyl, lowerhaloalkynyl, lower perhaloalkyl, lower perhaloalkoxy, lower haloalkoxy,and lower acyloxy; R₆ is selected from the group consisting ofhaloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy,S(O)_(m)C(R₇R₈)_(n)CF₃, and C(R₇R₈)_(n)CF₃; wherein W, X and Y areindependently chosen from the group consisting of S, O, N, NR₉ and CR₁₀and at least two of W, X and Y are heteroatoms; wherein R₇, R₈, and R₉are independently selected from the group consisting of hydrogen,fluoro, chloro, alkyl, perhaloalkyl, aryl, arylalkyl, heteroaryl andheteroarylalkyl, or together with the atoms to which they are attached,may be joined to form an optionally substituted 4- to 8-memberedheterocycioalkyl or an optionally substituted 3- to 8-memberedcycioalkyl ring, any of which may be optionally substituted as for R₁through R₅ and R₁₀; m is an integer between 0 and 2; and n is an integerbetween 0 and
 5. 11. The pharmaceutical composition of claim 1, whereinR₁ through R₅ are, independently, hydrogen, CN, F, Cl, Br, hydroxy,alkyl, alkoxy, hydroxyalkyl, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, carbamoyloxy, alkylamino,haloalkyl, perhaloalkyl, perhaloalkoxy, alkylthio, alkylthioalkyl,alkylsulfonyl, cycloalkylsulfonyl, or cycloalkylalkylsulfonyl, any ofwhich may be optionally substituted with halogen, alkoxy,perhalo-C₁-C₃-alkyl, or C₁-C₃ alkyl; R₆ is selected from the groupconsisting of perhaloalkyl, S(O)_(m)C(R₇R₈)_(n)CF₃, and C(R₇R₈)_(n)CF₃;R₇, R₈, and R₉ are independently selected from the group consisting ofhydrogen, fluoro, chloro, alkyl, and perhaloalkyl, any of which may beoptionally substituted; R₁₀ is selected from the group consisting ofhydrogen, CN, NO₂, F, Cl, Br, alkyl, cycloalkyl, cycloalkylalkyl,alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkylalkoxy, acyl,alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl,heteroaryloxycarbonyl, heteroarylalkoxycarbonyl, carbamoyl, alkylamino,amido, alkylamido, dialkylamido, perhaloalkyl, alkylthio,alkylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl,alkylsulfonamido, aryl, arylalkyl, aryloxy, arylalkoxy, arylthio,arylalkylthio, arylamino, arylalkylamino, heteroaryl, heteroarylalkyl,heteroaryloxy, heteroarylalkoxy, heteroarylamino, heteroarylalkylamino,heteroarylthio, heteroarylalkylthio, heteroarylalkylamino,heterocycloalkyl, heterocycloalkenyl, heterocycloalkoxy, andheterocycloalkenyloxy; and n is an integer between 0 and
 2. 12. Thepharmaceutical composition of claim 11, wherein: R₁, R₂, and R₃ are,independently, hydroxy, acyloxy, aroyloxy, arylalkanoyloxy,arylalkenoyloxy, heteroaroyloxy, heteroarylalkanoyloxy,heteroarylalkenoyloxy, alkoxycarbonyloxy, or carbamoyloxy, any of whichmay be optionally substituted; R₆ is selected from the group consistingof perhaloalkyl and C(R₇R₈)—CF₃; R₇ and R₈ are independently selectedfrom the group consisting of hydrogen, fluoro, and chloro; and R₁₀ isselected from the group consisting of hydrogen, CN, NO₂, F, Cl, Br,alkyl, cycloalkyl, cycloalkoxy, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylthio, alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heteroarylthio,heteroarylalkylthio, heterocycloalkyl, and heterocycloalkenyl.
 13. Thepharmaceutical composition of claim 12 comprising a compound of FormulaII or III or V or VI or VII or VIII or IX or X or XI or XII or XIII orXVI or XVII or XVIII or XIX

wherein: R₁₀ is selected from the group consisting of hydrogen, CN, NO₂,F, Cl, Br, alkyl, cycloalkyl, acyl, alkoxycarbonyl, aryloxycarbonyl,heteroaryloxycarbonyl, carbamoyl, amido, dialkylamido, perhaloalkyl,alkylsulfonyl, alkylsulfonylalkyl, cycloalkylsulfonyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkenyl.14. The pharmaceutical composition of claim 1, wherein the compound isof Formula IV

wherein: R₁₀ is selected from the group consisting of hydrogen, CN, NO₂,F, Cl, alkyl, aryloxycarbonyl, heteroaryloxycarbonyl, carbamoyl, amido,dialkylamido, perhaloalkyl, alkylsulfonyl, alkylsulfonylalkyl,cycloalkylsulfonyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocycloalkyl, and heterocycloalkenyl; and with the proviso that whenR₄ is Br, R₁₀ may not be unsubstituted phenyl.
 15. The pharmaceuticalcomposition of claim 1, wherein the salt is selected from the groupconsisting of acetate, adipate, alginate, aspartate, benzoate,benzenesulfonate, bisulfate, butyrate, citrate, camphorate,camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate,ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate,hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide,hydroiodide, 2-hydroxyethanesulfonate, lactate, malate, maleate,methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate,thiocyanate, tosylate, undecanoate, lithium, sodium, calcium, potassium,aluminum, ammonium, tetraethylammonium, methylammonium,dimethylammonium, N-methylmorpholinium, and ethanolammonium.
 16. Thepharmaceutical composition of claim 1, wherein the pharmaceuticalcomposition is a solid.
 17. The method of claim 5, wherein the patientis a human.
 18. The method of claim 9, wherein the patient is a human.